Transcription of the caveolin-1 gene is differentially regulated in lung type I epithelial and endothelial cell lines. A role for ETS proteins in epithelial cell expression

J Biol Chem. 2004 Jul 16;279(29):30028-36. doi: 10.1074/jbc.M402236200. Epub 2004 May 10.

Abstract

In the lung, caveolin-1 is expressed in both type I alveolar epithelial and endothelial cells where it is hypothesized to modulate molecular signaling activities and progression of tumorigenesis. Developmentally, caveolin-1alpha is expressed in fetal lung endothelial, but not epithelial, cells; in adult lung, both cell types express caveolin-1alpha. To test the hypothesis that caveolin-1 transcription is differentially regulated in type I and endothelial cells, we characterized the proximal promoter of the mouse caveolin-1 gene in lung cell lines to identify factors that control its cell-specific expression. We show that caveolin-1 expression is regulated by an Ets cis-element in a lung epithelial cell line, but not a lung endothelial cell line, and that three ETS family members, ETS-1, PEA3, and ERM, recognize and bind the Ets site in the epithelial cell line. Based on these findings, we have identified the Ets cis-element as a region that accounts for differential transcriptional regulation of caveolin-1 in lung epithelial and endothelial cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Blotting, Western
  • Caveolin 1
  • Caveolins / biosynthesis*
  • Caveolins / genetics*
  • Cell Line
  • Cell Nucleus / metabolism
  • DNA / chemistry
  • DNA Mutational Analysis
  • DNA Primers / pharmacology
  • DNA-Binding Proteins / metabolism
  • Endothelial Cells / metabolism*
  • Enhancer Elements, Genetic
  • Gene Deletion
  • Lung / cytology
  • Mice
  • Mutation
  • Oligonucleotides / chemistry
  • Polymerase Chain Reaction
  • Precipitin Tests
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Isoforms
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transfection

Substances

  • Cav1 protein, mouse
  • Caveolin 1
  • Caveolins
  • DNA Primers
  • DNA-Binding Proteins
  • Ets1 protein, mouse
  • Etv5 protein, mouse
  • Oligonucleotides
  • Protein Isoforms
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger
  • Transcription Factors
  • transcription factor PEA3
  • DNA